The present invention relates to a method and apparatus for estimating systolic and mean pulmonary artery pressures of a patient. More specifically, the invention relates to converting the second heart sound signal contained in the phonocardiagram (PCG) into a pulmonary artery pressure estimate.
Pulmonary hypertension is a disease characterized by a progressive and sustained elevation of pulmonary artery pressure (PAP). Pulmonary hypertension is a common and serious complication of multiple cardiovascular and respiratory diseases. Acquired heart diseases lead to pulmonary hypertension by increasing pulmonary blood flow or by increasing pulmonary venous pressure, which is the most common cause of pulmonary hypertension. Congenital heart diseases associated with left-to-right shunts or abnormal communication between the great vessels are commonly associated with pulmonary hypertension and intrinsic pulmonary diseases, respiratory disorders, can also lead to pulmonary hypertension. Among the respiratory disorders are the syndrome of alveolar hypoventilation and sleep apnea. Among the intrinsic lung diseases are chronic obstructive pulmonary disease, chronic obstruction of upper airways, diseases limiting pulmonary expansion and respiratory distress syndrome.
The major consequence of pulmonary hypertension is right ventricular failure. Pulmonary hypertension is an important risk factor for morbidity and mortality in patients with cardiovascular or respiratory diseases. In patients with primary pulmonary hypertension, the median survival time is 2.8 years. With the onset of right ventricular failure, patient survival is generally limited to approximately 6 months. Early detection and regular monitoring of pulmonary hypertension in patients is therefore essential to adjust the medical treatment and determine optimal timing for surgery. As the options available for treating pulmonary hypertension have increased, the requirement for accurate and noninvasive methods allowing regular and safe estimation of PAP has also increased.
Pulmonary hypertension is a serious cardiovascular dysfunction that is difficult to assess noninvasively. The PAP is usually measured using a pulmonary arterial catheter, Swan-Ganz catheter, in patients necessitating continuous monitoring of PAP. However, this method can cause several complications including lesions of the tricuspid valve, pulmonary valve, right ventricle, or pulmonary arteries, cardiac arrhythmia, dislodgment of a thrombus and infectious complications. This method is not recommended for repeated measurements, one time every week or month or 6 months depending of the evolution of the disease, because of the potential risks for the patient. Since regular evaluation of the PAP is very important for the follow up of the evolution of the disease and for the assessment of the efficacy of the treatment, noninvasive methods have been developed to allow frequent and accurate measurement of PAP.
Doppler echocardiography has been used for non-invasive estimation of the systolic PAP when tricuspid regurgitation can be detected as described by Nishimura, R. A. and Tajik, A. J., xe2x80x9cQuantitative hemodynamics by Doppler echocardiography: A noninvasive alternative to cardiac catheterization,xe2x80x9d Prog Cardiovasc Dis, vol. 36, no. 4, pp. 309-342, 1994. The right ventricular systolic pressure can be calculated by adding the systolic pressure gradient across the tricuspid valve, measured by using continuous-wave Doppler to the estimated right atrial pressure. The atrial pressure is set to 14 mm Hg when the jugular venous pressure is normal or mildly elevated and 20 mm Hg when the jugular pressure is markedly elevated. When the jugular venous pressure is not available, it is recommend to use 5, 10, or 20 mm Hg to estimate the right atrial pressure depending on the degree of collapse of the inferior vena cava during inspiration. Recently, it was demonstrated that the right atrial pressure may be estimated with reasonable accuracy, r=0.75, using the tricuspid E/Ea ratio, where E is the tricuspid inflow velocity of the E wave measured by pulsed Doppler and Ea is the tricuspid annulus velocity measured by tissue Doppler at early diastole. Furthermore, the systolic pressure gradient across the pulmonary valve must be either negligible or estimated by Doppler and added to the tricuspid gradient and right atrial pressure. This noninvasive method can provide a high degree of correlation, 0.89xe2x89xa6rxe2x89xa60.97, and a standard error (SEE) varying from 7 to 12 mmHg in comparison with pulmonary artery catheterization, systolic PAP range: 20-160 mmHg.
However, the estimation of PAP by Doppler echocardiography has several important limitations. Firstly, the PAP cannot be estimated by Doppler in approximately 50% of patients with normal PAP, 10% to 20% of patients with elevated PAP, and 34% to 76% of patients with chronic obstructive pulmonary disease because of the absence of tricuspid regurgitation, a weak Doppler signal or poor signal-to-noise ratio. To improve the feasibility of the method in patients with a weak Doppler signal or poor signal-to-noise ratio, it is necessary to use contrast agent enhancement. Secondly, Doppler echocardiography tends to overestimate PAP in patients with normal PAP and significantly underestimates the PAP in patients with severe pulmonary arterial hypertension. One surprising limitation of the method is the relatively important standard error in contrast to the above mentioned high levels of correlation. This is due to various error contributions associated with the non zero angle of the Doppler beam with the flow, the approximate estimation of the right atrial pressure, the presence of obstruction and pressure loss in the right ventricular outflow tract or in the pulmonary valve in some patients, the non simultaneous measurement of Doppler and catheter measurements in some studies, the non simultaneous recording of peak atrial, peak ventricular and peak pulmonary arterial pressures in patients, the use of the modified Bernoulli equation, and other factors. Furthermore, Doppler echocardiography requires an expensive ultrasound system and a highly qualified technician. This method is thus not applicable for daily measurements of PAP in small clinics or at home.
Acoustic methods based on signal processing of the second heart sound, s2(t), have been studied for the estimation of PAP. The onset of the aortic, A2(t), and the pulmonary, P2(t), components of S2(t) marks the end of left and right ventricular systole and the beginning of left and right ventricular diastole, respectively. In patients with pulmonary hypertension, the intensity of P2(t) is accentuated and the delay of P2(t) in relation to A2(t) is increased due to the prolongation of right ventricular systole. Furthermore, the A2(t)xe2x88x92P2(t) splitting time interval, SI, is indirectly proportional to the heart rate. Hence Leung et al. have underlined in xe2x80x9cAnalysis of the second heart sound for diagnosis of paediatric heart disease,xe2x80x9d IEEE Proceedings Sci Meas Technol, vol. 145, no. 6, pp. 285-290, 1998, the importance of normalizing the SI with respect to the duration of the cardiac cycle to obtain valuable diagnostic information. The normalized SI (NSI) has been found to be 3.3xc2x11.8% in normal subjects whereas it was 5.2xc2x11.1% in patients with pulmonary stenosis, a condition resulting in pressure overload of the right ventricle and 5.9xc2x10.7% in patients with atrial septal defect, a condition resulting in volume overload of the right ventricle and the pulmonary circulation. However, the relationship between NSI and the pulmonary artery pressure has not been studied.
Several studies have been done on the relationship between the resonant frequency, Fp, and the quality factor, Q, of the spectrum of P2(t) and the systolic PAP measured by pulmonary artery catheterization. In the study of Aggio et al. xe2x80x9cNoninvasive estimation of the pulmonary systolic pressure from the spectral analysis of the second heart sound,xe2x80x9d Acta Cardiologica, vol. XLV, no. 3, pp. 199-202, 1990, performed with 23 patients with mitral stenosis or high PAP, a significant correlation, r=0.96 and SEE less than 5 mmHg, was found between Fp and Q and the systolic PAP. In the study of Longhini et al. xe2x80x9cA new noninvasive method for estimation of pulmonary arterial pressure in mitral stenosis,xe2x80x9d American Journal of Cardiology, vol. 68 pp. 398-401, 1991) a similar correlation, r=0.98 and SEE=4.2 mmHg, was found in 30 patients with mitral stenosis or a systolic PAP greater than 34 mmHg. This study also showed significant correlations with the mean, r=0.88, and diastolic, r=0.87, PAPs.
There is a U.S. Pat. No. 6,050,950 issued to Mohler on Apr. 18, 2000 and entitled xe2x80x9cPassive/non invasive systemic and pulmonary blood pressure measurementxe2x80x9d. In this patent, the systemic and pulmonary pressures are estimated by using a range of pressure/frequency curves collected from the second heart sound in a population sample. The main limitation of this approach is that, ideally, it requires a pre-calibration for each patient, i.e. the curves must be obtained invasively for each patient between the systemic pressure and the spectrum of A2(t) and between the pulmonary pressure and the spectrum of P2(t).
A retrospective study by Chen, D. et al. xe2x80x9cEstimation of pulmonary artery pressure by spectral analysis of the second heart sound,xe2x80x9d American Journal of Cardiology, vol. 78 pp. 785-789, 1996, was performed by our group with 89 patients with a bioprosthetic heart valve to test and validate the method mentioned above by Longhini et al. and Aggio et al. in comparison with Doppler. However, it was not possible to reproduce the results of these studies because of the use of different PCG recording systems and patient populations. However, a different relationship was found by using additional features from the spectra of S2(t) and A2(t). The correlation was very good, r=0.84, SEE=5 mmHg and p less than 0.0001. The systolic PAP was obtained by using the following equation: PAP=47+0.68 Fpxe2x88x924.4 Qxe2x88x9217 Fp/Faxe2x88x920.15 Fs, where Fs and Fa are the resonant frequencies of S2(t) and A2(t), respectively. Due to the dependence of the regressive equation on the patient population and PCG recording system, it became necessary to perform basic animal studies specifically designed to solve these limitations and find a relationship between S2(t) and the PAP that is sensitive and specific only to the PAP.
The above prior art revealed that it is difficult to convert the frequency content of P2(t) to provide an accurate estimate of the PAP that would be independent of the patient population and the PCG recording system.
An object of the present invention is to provide a non-invasive method and apparatus for estimating the systolic and pulmonary artery pressures of a patient with greater efficiency and precision than the methods and apparatus revealed by the prior art.
According to the present invention there is provided a method for estimating the systolic and mean pulmonary artery pressures of a patient, comprising the steps of:
(a) producing an electri c signal xS(t) representative of heart sounds of the patient;
(b) extracting second heart sound S2(t) from the signal produced in step (a);
(c) extracting pulmonary and aortic components P2(t) and A2(t) from S2(t);
(d) extracting a signal representative of mean cardiac interval from the signal produced in step (a);
(e) correlating the pulmonary and aortic components P2(t) and A2(t) to obtain a cross correlation function;
(f) measuring a splitting interval as the time of occurrence of the maximal value of the cross correlation function obtained in step (e);
(g) producing a normalized splitting interval by dividing the splitting interval obtained in step (f) by the mean cardiac interval obtained in step (d); and
(h) estimating the systolic and mean pulmonary artery pressures by means of predetermined regressive functions, said predetermined regressive functions describing relationships between the normalized splitting interval and the systolic and mean pulmonary artery pressures.
According to the present invention, there is also provided an apparatus for estimating systolic and mean pulmonary artery pressures of a patient, comprising:
first producing means for producing an electric signal xs(t) representative of heart sounds of the patient;
first extracting means for extracting second heart sound S2(t) from the signal produced by the first producing means;
second extracting means for extracting pulmonary and aortic components P2(t) and A2(t) from S2(t) extracted by the first extracting means;
third extracting means for extracting a signal representative of mean cardiac interval from the signal produced by the first producing means;
correlating means for correlating the pulmonary and aortic components P2(t) and A2(t) to obtain a cross correlation function;
measuring means for measuring a splitting interval as the time of occurrence of the maximal value of the cross correlation function obtained by the correlating means;
second producing means for producing a normalized splitting interval by dividing the splitting interval obtained from the measuring means by the mean cardiac interval obtained from the third extracting means; and
estimating means for estimating the systolic and mean pulmonary artery pressures by means of predetermined regressive functions, said predetermined regressive functions describing relationships between the normalized splitting interval and the systolic and mean pulmonary artery pressures.
Further objects, advantages and other features of the present invention will become more apparent upon reading of the following non-restrictive description of preferred embodiments thereof given for the purpose of exemplification only with reference to the accompanying drawings.